Defining Criteria for Choosing Corneal Neurotization in Neurotrophic Keratopathy: A Systematic Review Along with Practical Advices.

PURPOSE: To identify and harmonize preoperative inclusion and exclusion criteria for corneal neurotization (CN) in neurotrophic keratopathy (NK), describe how consistently they are reported, and summarize practical, clinic-ready guidance for selection and follow-up.

METHODS

Systematic review (PRISMA-2020; PROSPERO CRD420251117787) of human studies on CN for NK (databases searched July 18, 2025). Study-level eligibility criteria, disease stage, esthesiometry, chronicity thresholds, donor-nerve requirements, and stated exclusions were evaluated; risk of bias (ROBINS-I) and certainty (GRADE) were recorded.

RESULTS

Thirty-six studies (380 patients) were included; of these, 26 (72.2%) explicitly reported eligibility criteria. Most common inclusion criteria were refractory NK (92.3%), severe/objective corneal anaesthesia or Mackie III severity stage (69.2%), NK with intact donor territory (50.0%), and corneal epithelial instability (46.2%). Exclusion criteria were often not stated (76.9%); when present, they most often listed active infection/non-NK disease (38.5%), systemic unsuitability (34.6%), absent/abnormal donor nerve(s) (15.4%), and severe limbal stem cell deficiency (15.4%). Across studies, CN improved corneal protection and surface stability with sensory recovery over ~6-18 months and in vivo confocal microscopy evidence of nerve regrowth; visual acuity changes were variable. No randomized clinical trials were found; ROBINS-I was commonly moderate to serious, and overall certainty by GRADE was low.

CONCLUSIONS

This systematic review defined and harmonized preoperative inclusion and exclusion criteria for CN in NK. A minimum preoperative dataset, including disease stage, mapped corneal sensitivity, denervation timeline and etiology, donor-dermatome integrity, feasibility of tension-free coaptation, and ocular surface status, may guide referral timing, donor-feasibility-driven technique selection, and structured follow-up.